Within the last few years, several studies have demonstrated that NGF treatments can affect regeneration of nerve fibers, enhance glial response to nerve injury, and facilitate behavioral recovery from brain damage. Little is known about how NGF acts to promote its ameliorative effects on brain function and whether such behavioral and anatomical effects change with the developmental status of the subjects. This proposal is a multidisciplinary attempt to specify some of the psychobiological effects of intracerebral administration of NGF in rats of different ages. The first project is concerned with the question of where isotopically labelled NGF accumulates in intact rat brain, and whether there is a change in the distribution (or target sites) of the protein as a function of age. Once specific areas are defined, we will determine whether cerebral metabolism, as measured by 2-deoxyglucose technique (2-DG), is altered by NGF treatments. NGF has been shown to increase glucose utilization and it is important to know if: (1) functional neuronal activity is enhanced by NGF and (2), if sites of labelled NGF accumulation are the same as those showing enhanced metabolic activity following NGF treatment. In addition, we will determine if there are changes in the pattern of glucose uptake in brain-damaged (mature and senescent) animals treated with NGF or control solutions. There is evidence that NGF affects glial reaction to brain injury and this presents the possibility the NGF-glial relationship may be involved in behavioral recovery that follows NGF treatment. I propose to extend our preliminary findings that intracerebral NGF administration alters glial reactions to brain injury. Perhaps the most important part of this proposal, from a psychobiological perspective, is the attempt to determine behavioral consequences of NGF treatments in normal and brain-damaged rats of different ages. In the present plan, a series of behavioral tests that involve motor learning, motivational and discriminative learning problems will be employed to examine both short-and long-term behavioral consequences of NGF treatments in intact and brain-damaged rats.